Multipotent mesenchymal stem cells reduce interstitial fibrosis but do not delay progression of chronic kidney disease in collagen4A3-deficient mice

被引:204
作者
Ninichuk, V.
Gross, O.
Segerer, S.
Hoffmann, R.
Radomska, E.
Buchstaller, A.
Huss, R.
Akis, N.
Schloendorff, D.
Anders, H-J
机构
[1] Univ Munich, Ctr Nephrol, Med Polyclin, Munich, Germany
[2] Univ Cologne, Fac Med, Merheim Med Ctr, Cologne Gen Hosp,Dept Internal Med 1, Cologne, Germany
[3] Univ Munich, Max Von Pettenkofer Inst, Munich, Germany
[4] Univ Munich, Inst Pathol, D-8000 Munich, Germany
[5] Roche Diagnost GmbH, Penzberg, Germany
[6] Hal Univ, Dept Mol Biol & Genet, Istanbul, Turkey
关键词
mesenchymal stem cells; kidney; fibrosis; chronic kidney disease; progression;
D O I
10.1038/sj.ki.5001521
中图分类号
R5 [内科学]; R69 [泌尿科学(泌尿生殖系疾病)];
学科分类号
1002 ; 100201 ;
摘要
Multipotent mesenchymal stem or stromal cells (MSC) have shown to improve outcome of acute renal injury models, but whether MSC can delay renal failure in chronic kidney disease is not known. We injected primary MSC or saline into mice that lack the alpha 3-chain of type IV collagen (COL4A3), a model of chronic kidney disease with close similarities to human Alport disease. Weekly injections of MSC from week 6 to 10 of life prevented the loss of peritubular capillaries and reduced markers of renal fibrosis, that is, interstitial volume, numbers of smooth muscle actin-positive interstitial cells, and interstitial collagen deposits as compared to saline-injected COL4A3-deficient mice. However, renal function, that is, blood urea nitrogen, creatinine levels, proteinuria as well as survival of COL4A3-deficient mice were not affected by MSC injections. Although MSC were found to localize to kidneys of COL4A3-deficient mice after injection, differentiation into renal cells was not detected. However, MSC expressed growth factors, that is, vascular endothelial growth factor (VEGF) and bone morphogenetic protein-7 under basal culture conditions. In fact, VEGF mRNA levels were increased in kidneys of MSC-injected COL4A3-deficient mice and MSC supernatants enhance endothelial cell proliferation in vitro. Thus, weekly injections with MSC prevent loss of peritubular capillaries possibly owing to local production of growth factors rather than by differentiation into renal cells. The maintenance of interstitial vasculature is associated with less interstitial fibrosis but, is insufficient to delay renal failure and survival of COL4A3-deficient mice.
引用
收藏
页码:121 / 129
页数:9
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